Project Summary Obesity, a chronic imbalance in energy homeostasis between energy intake and energy expenditure, is a public health crisis and continues to be among the most important medical challenges in the U.S.A. Obesity creates a greater than $190 billion burden annually on American healthcare. The development of therapeutic approaches that lessen or eliminate obesity-associated morbidity and mortality would have a transformative impact on the American population and healthcare spending. There are two types of adipose tissue in mammals: white adipose tissue which is specialized for energy storage, and thermogenic adipose tissue specialized for energy expenditure and thermogenesis. Thermogenic adipose tissue has been shown to have an inverse correlation with adiposity, meaning that it might be possible to increase whole-body energy expenditure by increasing the number and/or activity of thermogenic adipose tissue. Thus, altering adipose thermogenic capacity could be a treatment for metabolic diseases, including obesity. New therapies targeting thermogenic adipose tissue have failed in maintaining transformed adipose tissue in-vivo, in part, due to the limited understanding of how environmental factors control adipocyte fate and maintenance. This research effort aims to understand the role of the extracellular matrix interaction (ECM) in the fate of adipocytes. This information will identify new therapeutic targets for obesity and metabolic diseases. A better understanding of the underlying causes of these characteristics for thermogenic fat will allow us to specifically manipulate these cells to improve systemic energy metabolism and glucose homeostasis, and to explore synthetic substrates that increase formation of thermogenic adipose tissue.